Identification of the transcriptional repression domain of the adenovirus type 5 E1B-55 kDa protein

The E1B-55 kDa protein of human adenovirus type 5 is known to function early in lytic infection by reversing growth arrest and apoptosis that result from E1A-induced accumulation and activation of the p53 cellular tumor suppressor. This function allows infected cells to survive long enough to produce high levels of progeny virions, and in the case of rodent cells it permits the formation of stable E1A transformants. The E1B-55 kDa protein binds to p53 and inhibits its ability to activate transcription. Inhibition of p53 appears to result from transcriptional repression activity associated with the E1B-55 kDa polypeptide. In the present studies using fusion products containing the DNA binding domain of Gal4 linked to a series of mutant E1B-55 kDa proteins, we have identified a domain towards its carboxy terminus that is responsible for repression. It may function directly as a repressor or it may bind to a cellular repressor that is targeted to p53-dependent promoters through interactions of the E1B-55 kDa protein with p53. This domain is also present in the 156-residue (156R) product of E1B, which is composed of the amino terminus 79 and carboxy terminus 77 amino acids of the E1B-55 kDa protein. Although 156R does not appear to bind to p53 in the in vivo experiments conducted here, its repression activity could be directed against other targets through a separate mechanism